Interpretive Summary: Obesity has been identified “one of today’s most blatantly visible – yet most neglected – public health problems.” This rising epidemic of overweight and obesity has been called by some as “globesity” to clearly reflect that is a global problem and that, unless action is taken, billions will suffer from debilitating conditions associated with this disorder. Overeating and sedentary lifestyle are major environmental factors determining the current globesity and consumption of certain foods (including dairy products) has been associated with different risk of obesity. However, genetic factors are also important to predispose some people to obesity. Moreover, genetic factors may also affect the ability to consume dairy products during adult life. We have studied genetic variants at the lactase (LCT) gene, that has been strongly associated with lactase persistence in Europeans in relation to obesity. Our data reveal that carriers of a certain form of the LCT gene had higher weight, body mass index (BMI) and waist circumference compared with non-carriers. However, the increased obesity risk can be modulated by lactose intake. Therefore, our data support a role of dairy products to normalize body weight in certain individuals defined by their LCT gene.

Technical Abstract:
The -13910C>T polymorphism (rs4988235) upstream from the lactase (LCT) gene, strongly associated with lactase persistence (LP) in Europeans, is emerging as a new candidate for obesity. We aimed to analyze the association of this polymorphism with obesity-related variables and its modulation by dairy product intake in an elderly population. We studied 940 high-cardiovascular risk Spanish subjects (aged 67 +/- 7 years). Dairy product consumption was assessed by a validated questionnaire. Anthropometric variables were directly measured, and metabolic syndrome-related variables were obtained. Prevalence of genotypes was: 38.0% CC (lactase nonpersistent (LNP)), 45.7% CT, and 16.3% TT. The CC genotype was not associated with lower milk or dairy product consumption in the whole population. Only in women was dairy intake significantly lower in CC subjects. The most important association was obtained with anthropometric measurements. CC individuals had lower weight (P = 0.032), lower BMI (29.7 +/- 4.2 vs. 30.6 +/- 4.2 kg/m2; P = 0.003) and lower waist circumference (101.1 +/- 11.8 vs. 103.5 +/- 11.5 cm; P = 0.005) than T-allele carriers. Obesity risk was also significantly higher in T-allele carriers than in CC individuals (odds ratio (OR): 1.38; 95% confidence interval (CI): 1.05–1.81; P = 0.01), and remained significant even after adjustment for sex, age, diabetes, physical activity, and energy intake. However, in subgroup analysis, these associations were found to be significant only among those consuming moderate or high lactose intakes (>8 g/day). No significant associations with lipids, glucose, or blood pressure were obtained after adjustment for BMI. In conclusion, despite not finding marked differences in dairy product consumption, this polymorphism was strongly associated with BMI and obesity and modulated by lactose intake in this Mediterranean population.